ArticleLeukemia2011
A genome-wide approach identifies that the aspartate metabolism pathway contributes to asparaginase sensitivity.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Expression and polymorphism (rs4880) of mitochondrial superoxide dismutase (SOD2) and asparaginase induced hepatotoxicity in adult patients with acute lymphoblastic leukemia.The pharmacogenomics journal · 2017Trial
- The impact of asparaginase phenotype-related single nucleotide polymorphisms on prognosis in pediatric B-cell precursor acute lymphoblastic leukemia.European journal of medical research · 2025Article
- The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran.Discover oncology · 2024Article
- Functional and pathologic association of aminoacyl-tRNA synthetases with cancer.Experimental & molecular medicine · 2022Review
- Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.Pharmacogenomics · 2021Review
- Roles of Aminoacyl-tRNA Synthetases in Cancer.Frontiers in cell and developmental biology · 2020Review
- SLC1A3 contributes to L-asparaginase resistance in solid tumors.The EMBO journal · 2019Article
- Pharmacogenetics of asparaginase in acute lymphoblastic leukemia.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious against Both T- and B-cell Acute Lymphoblastic LeukemiasCancer research · 2018Article
- Identification of a cytogenetic and molecular subgroup of acute myeloid leukemias showing sensitivity to L-Asparaginase.Oncotarget · 2017Article
- Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach.International journal of molecular sciences · 2017Article
- Amino acid auxotrophy as a system of immunological control nodes.Nature immunology · 2016Review
- Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Evaluating the role of admixture in cancer therapy via in vitro drug response and multivariate genome-wide associations.Pharmacogenomics · 2015Article
- Developing interventions for cancer-related cognitive dysfunction in childhood cancer survivors.Journal of the National Cancer Institute · 2014Review
- Identification of genetic variants or genes that are associated with Homoharringtonine (HHT) response through a genome-wide association study in human lymphoblastoid cell lines (LCLs).Frontiers in genetics · 2014Article
- Genetic and epigenetic variants contributing to clofarabine cytotoxicity.Human molecular genetics · 2013Article
- Metabolomics of the tumor microenvironment in pediatric acute lymphoblastic leukemia.PloS one · 2013Article
- Cancer pharmacogenomics: strategies and challenges.Nature reviews. Genetics · 2013Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Asparaginase is an important component for treatment of childhood acute lymphoblastic leukemia (ALL). The basis for interindividual differences in asparaginase sensitivity remains unclear. To comprehensively identify genetic variants important in the cytotoxicity of asparaginase, we used a genome-wide association approach using the HapMap lymphoblastoid cell lines (87 CEU trio members) and 54 primary ALL leukemic blast samples at diagnosis. Asparaginase sensitivity was assessed as the drug concentration necessary to inhibit 50% of growth (inhibitory concentration (IC)(50)). In CEU lines, we tested 2,390,203 single-nucleotide polymorphism (SNP) genotypes at the individual SNP (P<0.001) and gene level (P<0.05), and identified 329 SNPs representing 94 genes that were associated with asparaginase IC(50). The aspartate metabolism pathway was the most overrepresented among 199 pathways evaluated (P=8.1 × 10(-3)), with primary involvement of adenylosuccinate lyase and aspartyl-tRNA synthetase genes. We validated that SNPs in the aspartate metabolism pathway were also associated with asparaginase sensitivity in primary ALL leukemic blast samples (P=5.5 × 10(-5)). Our genome-wide interrogation of CEU cell lines and primary ALL blasts revealed that inherited genomic interindividual variation in a plausible candidate pathway can contribute to asparaginase sensitivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.